Most cited article - PubMed ID 35264712
Approach to map nanotopography of cell surface receptors
Studying the complex realm of cellular communication and interactions by fluorescence microscopy requires sample fixation on a transparent substrate. To activate T cells, which are pivotal in controlling the immune system, it is important to present the activating antigen in a spatial arrangement similar to the nature of the antigen-presenting cell, including the presence of ligands on microvilli. Similar arrangement is predicted for some other immune cells. In this work, immune cell-stimulating platform based on nanoparticle-ligand conjugates have been developed using a scalable, affordable, and broadly applicable technology, which can be readily deployed without the need for state-of-the-art nanofabrication instruments. The validation of surface biofunctionalization was performed by combination of fluorescence and atomic force microscopy techniques. We demonstrate that the targeted system serves as a biomimetic scaffold on which immune cells make primary contact with the microvilli-mimicking substrate and exhibit stimulus-specific activation.
- Keywords
- Biotechnology, Cell biology, Immunology,
- Publication type
- Journal Article MeSH
T cells communicate with the environment via surface receptors. Cooperation of surface receptors regulates T-cell responses to diverse stimuli. Recently, finger-like membrane protrusions, microvilli, have been demonstrated to play a role in the organization of receptors and, hence, T-cell activation. However, little is known about the morphogenesis of dynamic microvilli, especially in the cells of immune system. In this review, I focus on the potential role of lipids and lipid domains in morphogenesis of microvilli. Discussed is the option that clustering of sphingolipids with phosphoinositides at the plasma membrane results in dimpling (curved) domains. Such domains can attract phosphoinositide-binding proteins and stimulate actin cytoskeleton reorganization. This process triggers cortical actin opening and bundling of actin fibres to support the growing of microvilli. Critical regulators of microvilli morphogenesis in T cells are unknown. At the end, I suggest several candidates with a potential to organize proteins and lipids in these structures.
- Keywords
- T cell, dimpling domains, lipid rafts, membrane curvature, membrane-associated proteins, microvilli, phosphoinositides, sphingolipids,
- MeSH
- Cell Membrane chemistry metabolism MeSH
- Phosphatidylinositols metabolism MeSH
- Immunomodulation MeSH
- Humans MeSH
- Membrane Microdomains chemistry metabolism MeSH
- Lipid Metabolism * MeSH
- Microvilli metabolism ultrastructure MeSH
- Morphogenesis MeSH
- Sphingolipids metabolism MeSH
- Signal Transduction MeSH
- T-Lymphocytes cytology physiology ultrastructure MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Phosphatidylinositols MeSH
- Sphingolipids MeSH